Kiehl EL, 1,2 Parker AM, 1 Matar RM, 2 Gottbrecht M, 1 Johansen MC, 1 Adams MP, 1 Griffiths LA, 2 Bidwell KL, 1 Menon V, 2 Enfield KB, 1 Gimple LW 1

Transcription

1 C-GRApH: A Validated Scoring System For The Early Risk Stratification Of Neurologic Outcomes After Out-of-hospital Cardiac Arrest Treated With Therapeutic Hypothermia Kiehl EL, 1,2 Parker AM, 1 Matar RM, 2 Gottbrecht M, 1 Johansen MC, 1 Adams MP, 1 Griffiths LA, 2 Bidwell KL, 1 Menon V, 2 Enfield KB, 1 Gimple LW 1 University of Virginia, Charlottesville, VA, USA; 1 Cleveland Clinic Foundation, Cleveland, OH, USA; 2

2 Background Estimated 326,000 out-of-hospital cardiac arrests (OHCA) in US in 2015 Survival to hospital discharge: 10% Neurologic injury is the leading cause of death (67%) and results in significant disability in survivors Therapeutic hypothermia (TH)/targeted temperature management (TTM) improves neurologic outcomes after OHCA Ventricular tachycardia/fibrillation (class I): 20% absolute risk reduction Pulseless electrical activity/asystole (class IIb): 5% relative risk reduction

3 Background Early prognosis after OHCA is problematic due to decreased specificity of prior gold-standard testing in the TH/TTM population Current consensus recommendation: delay prognosis >72 hours Given high morbidity/mortality even with TH/TTM, ethical (prolonged suffering for patients/families) and economic incentives exist for reliable early risk stratification Multiple past scoring systems (e.g. OHCA, 5-R) developed to predict neurologic outcomes after OHCA at hospital presentation Not validated in TH/TTM population Heavily dependent on unreliable timing variables (e.g. time from arrest to return of spontaneous circulation)

4 Study Goals To develop and validate a scoring system that effectively stratifies neurologic outcomes following out-of-hospital cardiac arrest in the TH/TTM population that: 1. Uses only objective data available at initial hospital presentation 2. Eliminates the use of unreliable timing variables 3. Is applicable to OHCA patients regardless of presenting rhythm 4. Can be easily calculated at the bedside by various sub-specialty providers that participate in post-ohca care

5 Development Cohort Retrospective review of the prospectively-acquired, consecutive University of Virginia CCU OHCA database from (n = 122) Inclusion criteria Adult (age 18), resuscitated, non-traumatic OHCA Intention to treat with TH/TTM at o C for 24 hours Primary outcome: favorable neurologic outcome at hospital discharge Definition: Glasgow-Pittsburgh cerebral performance category (CPC) 1-2 CPC 1-2: Mild-moderate cerebral disability; able to perform ADLs independently CPC 3: Severe cerebral disability; Dependent on others for ADLs CPC 4: Vegetative state CPC 5: Death Retrospective assignment by consensus of blinded neurologists based on documented physical exam findings and consultation notes

6 Development Cohort Patient data at hospital presentation (demographics, pre-ohca diagnoses, arrest characteristics, laboratory results) were compared between favorable (CPC 1-2) and poor (CPC 3-5) neurologic outcome groups Uni-variable logistic regression then performed with variables satisfying an a priori ρ<0.1 cutoff between outcome groups retained for multi-variable analysis (cut points identified for continuous variables) Stepwise multi-variable logistic regression then performed to eliminate variable co-dependence and create a composite scoring system with maximized c-statistic

7 Development Cohort Characteristics CPC 1-2 (n = 33) CPC 3-5 (n = 89) P-value Age 52.6 ± ± Sex (male) 73% 66% 0.57 Pre-OHCA coronary artery disease 21% 47% Congestive heart failure 15% 31% Diabetes mellitus 18% 38% COPD 3% 21% Stage III chronic kidney disease 6% 17% Ventricular tachycardia/fibrillation 97% 56% <0.001 Time to CPR (min) 2.5 ± ± Time to EMS (min) 7.7 ± ± Time to ROSC (min) 20.6 ± ± 17.5 <0.001 Arterial ph 7.20 ± ± Lactic acid (mmol/l) 5.6 ± ± Troponin I (ng/ml) 0.71 ± ± Blood Glucose (mg/dl) 243 ± ±

8 C-GRApH Variables (1 point each, equally weighted) C: Coronary artery disease (CAD), pre-arrest Definition: history of prior MI, CABG, PCI, or obstructive lesion >50% on cardiac catheterization (not chart diagnosis alone) NOT included if CAD diagnosed during OHCA hospitalization G: Glucose (blood) > 200 mg/dl Fingerstick, blood gas, or metabolic panel R: Rhythm of arrest NOT ventricular tachycardia (VT) or fibrillation (VF) If AED only rhythm discriminator, shockable = VT/VF A: Age > 45 years ph: ph (arterial) < 7.0 Scoring system ranging from 0 to 5 with higher score predictive of worse neurologic outcome C-statistic:.818 (95% CI , ρ<0.001)

9 Validation Cohort Combination of internal and external cohorts (n = 344) Internal (n= 72) Consecutive new, prospective cohort from University of Virginia OHCA database from External (n = 272) Consecutive retrospective review of prospectively-acquired Cleveland Clinic Foundation OHCA database from CCU, MICU, NNICU, SICU settings Main academic center and satellite community hospitals CPC scores assigned prospectively Other ICU 42% CCU 58% Community 39% Academic 61%

10 Characteristics of Development vs. Validation Cohorts Development Cohort (n = 122) Validation Cohort (n = 344) P Value Survival 42 (34%) 110 (32%) CPC 3.8 (1.7) 4 (1.5) C-GRApH Score 2.4 (1.0) 2.8 (1.1) Death/Withdrawal <72 hrs 43 (35%) 85 (25%) Witnessed Arrest 104 (85%) 265 (77%) Bystander CPR 70 (57%) 162 (47%) Time to ROSC (min) 30.3 (17.2) 26.7 (17.3) Male Gender 83 (68%) 194 (56%) CAD 49 (40%) 117 (34%) Glucose (mg/dl) 290 (119) 268 (127) VT/VF 82 (67%) 129 (38%) <0.001 Age 59.7 (15.5) 62.3 (15.2) Arterial ph 7.17 (0.15) 7.15 (0.19) 0.165

11 Receiver Operating Characteristic

12 Neurologic Outcomes Stratified by C-GRApH Score

13 Neurologic Outcomes by C-GRApH Score in Development, Validation, and Composite Cohorts Favorable Neurologic Outcome by C-GRApH Score Development (n = 122) Validation (n = 344) Composite (n = 466) 100% Favorable Neurologic Outcome 90% 80% 70% 60% 50% 40% 30% 20% 10% 0% N = 10 N = 50 N = 130 N = 177 N = 85 N = C-GRApH Score

14 Study Limitations & Future Directions Study Limitations Partially retrospective Small sample sizes at score extremes Future Directions Fully prospective, multi-site validation Long-term follow-up of neurologic outcomes and quality of life assessment

15 Conclusions C-GRApH provides excellent stratification of neurologic outcomes following OHCA in patients treated with TH/TTM using objective data available at hospital presentation Nearly identical ROC (c-statistic 0.82, p<0.001) and stratification by score in both the development and validation cohorts Applicable to varied ICU and hospital settings Simple pneumonic that is easy to use Provides early objective outcome data to aid in family discussions Identifies a patient cohort (score 4) that derives little to no benefit from TH/TTM, aggressive intervention, and ICU care following OHCA

16 Questions?